Knockout mice for pharmacological screening: testing the specificity of Na+-Ca2+ exchange inhibitors.

Reuter, Hannes; Henderson, Scott A; Han, Tieyan; Matsuda, Toshio; Baba, Akemichi; Ross, Robert S; Goldhaber, Joshua I; Philipson, Kenneth D · Circ Res · 2002

basic_science · Level V

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Abstract

The role of the Na+-Ca2+ exchanger as a major determinant of cell Ca2+ is well defined in cardiac tissue, and there has been much effort to develop specific inhibitors of the exchanger. We use a novel system to test the specificity of two putative specific inhibitors, KB-R7943 and SEA0400. The drugs are applied to electrically stimulated heart tubes from control mouse embryos or embryos with the Na+-Ca2+ exchanger knocked out. We monitored effects of the drugs on Ca2+ transients. Both drugs depress the Ca2+ transients at low concentrations even in the absence of any Na+-Ca2+ exchanger. KB-R7943 and SEA0400 are not completely specific and should be used with caution as Na+-Ca2+ exchange inhibitors.

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